Pediatric Enterocolotis and Hirschsprung's Disease

Key Faculty:

  • Philip Frykman, MD, PhD

 


Enterocolitis and Hirschsprung’s Disease - Philip Frykman, MD, PhD

The laboratory is interested in why some children with Hirschsprung disease (HD) develop severe enterocolitis after surgical correction while others don’t.  To study this problem, the research team developed an animal model of this condition using Endothelin Receptor B-null (Ednrb-/-) mice with colonic aganglionosis.  Serendipitously, we found that the Ednrb-/- mice with enterocolitis also have small spleens, and our further characterization has found marked bone marrow and splenic lymphopenia, as well as premature thymic involution.  Our work suggests that ET-3-Ednrb signaling plays a critical role for normal lymphocyte and lymphoid organ development in mice. Going forward, we plan to use our model to investigate the mechanisms by which ET-3-Ednrb signalling leads to lymphopenia and enterocolitis.

Selected Publications:

  • Zhao, L., Cheng, Z., Dhall, D., Doherty, T.M., Frykman, P.K.  (2009) A novel corrective pullthrough surgery in a mouse model of Hirschsprung’s Disease. J. Pediatr Surg. 44(4), 759-766. PMID: 19361637
  • Zhao, L., Dhall, D., Cheng, Z., Wang, H.L., Doherty, T.M., Bresee, C., Frykman, P.K.  (2010) Murine model of Hirschsprung-associated enterocolitis II: Surgical correction of aganglionosis does not eliminate enterocolitis. J Pediatr Surg. 45(1), 206-212.  PMID: 20106505
  • Cheng, Z., Dhall, D., Zhao, L., Wang, H.L., Doherty, T.M., Bresee, C., Frykman, P.K. (2010) Murine model of Hirschsprung-associated enterocolitis I: Phenotypic characterization with development of a histopathological grading system. J Pediatr Surg. 45(3), 475-482. PMID: 20223308 PubMed in process